Effects of moxa smoke through olfactory pathway on learning and memory ability in rapid aging mice / 中国针灸

OBJECTIVE@#To observe the effects of moxa smoke through olfactory pathway on learning and memory ability in rapid aging (SAMP8) mice, and to explore the action pathway of moxa smoke.@*METHODS@#Forty-eight six-month-old male SAMP8 mice were randomly divided into a model group, an olfactory dysfunction group, a moxa smoke group and an olfactory dysfunction + moxa smoke group, with 12 mice in each group. Twelve age-matched male SAMR1 mice were used as the blank group. The olfactory dysfunction model was induced in the olfactory dysfunction group and the olfactory dysfunction + moxa smoke group by intraperitoneal injection of 3-methylindole (3-MI) with 300 mg/kg, and the moxa smoke group and the olfactory dysfunction + moxa smoke group were intervened with moxa smoke at a concentration of 10-15 mg/m3 for 30 min per day, with a total of 6 interventions per week. After 6 weeks, the emotion and cognitive function of mice was tested by open field test and Morris water maze test, and the neuronal morphology in the CAI area of the hippocampus was observed by HE staining. The contents of neurotransmitters (glutamic acid [Glu], gamma-aminobutyric acid [GABA], dopamine [DA], and 5-hydroxytryptamine [5-HT]) in hippocampal tissue of mice were detected by ELISA.@*RESULTS@#The mice in the blank group, the model group and the moxa smoke group could find the buried food pellets within 300 s, while the mice in the olfactory dysfunction group and the olfactory dysfunction + moxa smoke group took more than 300 s to find them. Compared with the blank group, the model group had increased vertical and horizontal movements (P<0.05) and reduced central area residence time (P<0.05) in the open field test, prolonged mean escape latency on days 1-4 (P<0.05), and decreased search time, swimming distance and swimming distance ratio in the target quadrant of the Morris water maze test, and decreased GABA, DA and 5-HT contents (P<0.05, P<0.01) and increased Glu content (P<0.05) in hippocampal tissue. Compared with the model group, the olfactory dysfunction group had increased vertical movements (P<0.05), reduced central area residence time (P<0.05), and increased DA content in hippocampal tissue (P<0.05); the olfactory dysfunction + moxa smoke group had shortened mean escape latency on days 3 and 4 of the Morris water maze test (P<0.05) and increased DA content in hippocampal tissue (P<0.05); the moxa smoke group had prolonged search time in the target quadrant (P<0.05) and increased swimming distance ratio, and increased DA and 5-HT contents in hippocampal tissue (P<0.05, P<0.01) and decreased Glu content in hippocampal tissue (P<0.05). Compared with the olfactory dysfunction group, the olfactory dysfunction + moxa smoke group showed a shortened mean escape latency on day 4 of the Morris water maze test (P<0.05). Compared with the moxa smoke group, the olfactory dysfunction + moxa smoke group had a decreased 5-HT content in the hippocampus (P<0.05). Compared with the blank group, the model group showed a reduced number of neurons in the CA1 area of the hippocampus with a disordered arrangement; the olfactory dysfunction group had similar neuronal morphology in the CA1 area of the hippocampus to the model group. Compared with the model group, the moxa smoke group had an increased number of neurons in the CA1 area of the hippocampus that were more densely packed. Compared with the moxa smoke group, the olfactory dysfunction + moxa smoke group had a reduced number of neurons in the CA1 area of the hippocampus, with the extent between that of the moxa smoke group and the olfactory dysfunction group.@*CONCLUSION@#The moxa smoke could regulate the contents of neurotransmitters Glu, DA and 5-HT in hippocampal tissue through olfactory pathway to improve the learning and memory ability of SAMP8 mice, and the olfactory is not the only effective pathway.

Protective effects of taurine on learning and memory impairment after exposure to formaldehyde and benzene analogues in young rats / 环境与职业医学

Background Formaldehyde and benzene homologues are common environmental pollutants, and their neurotoxicity has aroused widespread concern. Objective To investigate the effect of taurine on cognitive impairment after exposure to formaldehyde and benzene analogues in young rats. Methods Twenty four-week old SD rats were randomly divided into four groups, with six rats in each group: control group (clean air), model group (5 mg·m−3 formaldehyde + 5 mg·m−3 benzene + 10 mg·m−3 toluene + 10 mg·m−3 xylene), low-dose taurine intervention group (5 g·L−1 taurine + mixture of formaldehyde and benzene analogues), and high-dose taurine intervention group (10 g·L−1 taurine + formaldehyde and mixture of benzene analogues), and the exposure was administered by oral and nasal aerosol inhalation for 28 d. At the end of exposure, the learning and memory ability of rats in each group was measured by Morris water maze test. After the behavioral test, the rats were anesthetized and neutralized, and the brain tissue was harvested for histopathological and molecular biological tests. The apoptosis rate of neurons in hippocampal CA1 area was detected by Tunel assay, and the expression levels of apoptosis-related proteins such as caspase 3, bax, and bcl-2 in hippocampal tissue were detected by Western blotting. Results The growth and development of rats in each group were good during inhalation. During the Morris water maze experiment, the escape latencies of rats in the taurine intervention groups were not different from that in the control group (P>0.05) from day 3 to day 5 of training, while the escape latency of rats in the model group was significantly higher than that in the control group (P <0.05). The number of crossing platform and the target quadrant residence time in the high-dose taurine intervention group were not different from those in the control group (P>0.05), while the two variables in the model group and low-dose taurine intervention group were significantly lower than those in the control group (P <0.05). The apoptotic rates of neurons in the hippocampal CA1 area of rats in the control group, model group, and low-dose and high-dose taurine intervention groups were 5.11%, 18.87%, 9.39%, and 4.63%, respectively. The apoptotic rate in the model group was higher than those in the control group and low-dose and high-dose taurine intervention groups (P<0.05). The expression levels of caspase 3, bax, and bcl-2 in the hippocampus of rats in the low-dose and high-dose taurine intervention groups showed no difference compared with the control group (P>0.05). The expression levels of caspase 3 and bax in the model group were higher than those in the control group and low-dose or high-dose taurine intervention groups (P<0.05), and the expression levels of bcl-2 was lower (P<0.05). Conclusion The mixed exposure to formaldehyde and benzene analogues can damage the learning and memory ability of young rats, and increase the apoptosis of neurons in hippocampal CA1 region. Taurine can reverse the damage induced by formaldehyde and benzene analogues.

Effects of subchronic exposure to benzoɑpyrene on memory function and mRNA expressions of NMDA receptors in different brain regions in rats / 环境与职业医学

Background The altered expressions of hippocampal N-methyl-D-aspartate (NMDA) receptors induced by benzo[ɑ]pyrene (BaP) causes short-term spatial learning and memory impairment in humans and animals, but whether BaP causes alterations of NMDA receptor subunits in other brain regions and the associated neurotoxic mechanism is still essentially unknown. Objective To observe the mRNA expressions of NR1, NR2A, and NR2B of NMDA receptor subunits in different brain regions in SD rat model with subchronic exposure to BaP, and to provide a basis for in-depth study of the mechanism of BaP-induced neurotoxicity. Methods Forty male SD rats were selected and randomly divided into a control group and 1.00, 2.50, and 6.25 mg·kg−1 BaP exposure groups with 10 rats in each group. The exposure rats received intraperitoneal injection of BaP every other day for 90 d.The average latency to platform, the average total distance, and the duration spent in previous quadrant were measured by the Morris Water Maze. Real-time fluorescence quantitative PCR was used to detect the mRNA expressions of NR1, NR2A, and NR2B in hippocampus, cortex, cerebellum, and striatum of rats. Results The average latency to platform and the average total distance in the 2.50 and 6.25 mg·kg−1 BaP groups were significantly prolonged compared with the control group (P<0.05), and the duration that rats spent in previous quadrant in the 6.25 mg·kg−1 BaP group was significantly shortened (P<0.05). Compared with the control group, the mRNA expressions of NR1 and NR2B in the hippocampus in the 2.50 and 6.25 mg·kg−1 BaP groups were significantly reduced (P<0.05), and the NR2A mRNA expression in the hippocampus in the 6.25 mg·kg−1 BaP group was significantly reduced (P<0.05); the mRNA expressions of NR1 and NR2B in the cortical tissue in the 6.25 mg·kg−1 BaP group were significantly reduced (P<0.05), and the mRNA expression of NR2A in the cortical tissue in the 1.00 mg·kg−1 BaP group was reduced; the mRNA expression of NR2B in the cerebellar tissue in the 6.25 mg·kg−1 BaP group was significantly reduced (P<0.05); there were no differences in the mRNA expressions of NMDA receptor subunits in the striatum tissue (P>0.05). Conclusion Subchronic BaP exposure can cause short-term spatial learning and memory impairment in rats, which may be related to the down-regulation of mRNA expressions of NR1, NR2A, and NR2B in hippocampus, changes of mRNA expressions of NR1, NR2A, and NR2B in cortical area, and the down-regulation of NR2B mRNA expression in cerebellum.

Mechanism of Kaixinsan on Learning and Memory Ability and Synaptic Function of APP/PS1 Mice / 中国实验方剂学杂志

Objective:To explore the underlying protective mechanism of Kaixinsan on learning， memory， and synaptic function in APP/PS1 mice. Method:Sixty APP/PS1 mice were randomly divided into a model group， a donepezil （2 mg·kg^-1·d^-1） group， and low- （0.7 g·kg^-1·d^-1）， medium- （1.4 g·kg^-1·d^-1）， and high-dose （2.8 g·kg^-1·d^-1） Kaixinsan groups， and the wild-type mice of the same age in the same litter were assigned to the normal group， with 12 mice in each group. After continuous intragastric administration for two months， the Morris water maze experiment was performed. The ultrastructure of hippocampal neurons was observed by transmission electron microscopy. The colorimetric assay was used to detect serum content of acetylcholine （ACh）， choline acetyltransferase （ChAT）， acetylcholinesterase （AChE）， and levels of hippocampal reactive oxygen species （ROS）， malondialdehyde （MDA）， superoxide dismutase （SOD）， and glutathione peroxidase （GSH-Px）. Real-time fluorescence-based quantitative polymerase chain reaction （Real- time PCR） was used to detect the mRNA expression of hippocampal brain-derived neurotrophic factor （BDNF）， beta-nerve growth factor （NGFB）， discs large homolog (DLG)2， DLG4， and synaptophysin （SYP）. Result:Compared with the normal group， the model group showed prolonged escape latency， reduced number of crossing platforms， shortened stay in the target quadrant （<italic>P</italic><0.01）， decreased number of mitochondria with different shapes and irregular arrangement， some swollen and deformed mitochondria with broken mitochondrial cristae， endolysis， and cytoplasm vacuole， and more cell debris. Additionally， the model group also displayed reduced serum levels of ACh and ChAT， increased AChE （<italic>P</italic><0.01）， elevated hippocampal ROS and MDA （<italic>P</italic><0.05，<italic>P</italic><0.01）， declining SOD and GSH-Px （<italic>P</italic><0.01）， and diminished hippocampal BDNF， NGFB， DLG2， DLG4， and SYP mRNA levels （<italic>P</italic><0.05，<italic>P</italic><0.01）. Compared with the model group， the donepezil group， and the medium- and high-dose Kaixinsan groups showed shortened escape latency， increased number of crossing platforms， prolonged stay in the target quadrant （<italic>P</italic><0.05，<italic>P</italic><0.01）， improved mitochondrial damage with a regular shape （mainly oval shape）， relieved mitochondrial swelling and deformation， and clear mitochondrial cristae. Furthermore， the donepezil group， and the medium- and high-dose Kaixinsan groups also exhibited increased serum ACh and ChAT levels （<italic>P</italic><0.05，<italic>P</italic><0.01）， blunted AChE activity （<italic>P</italic><0.05）， reduced hippocampal ROS level （<italic>P</italic><0.05，<italic>P</italic><0.01）， declining MDA level （<italic>P</italic><0.05）， potentiated SOD and GSH-Px activities， and up-regulated hippocampal BDNF， NGFB， DLG2， DLG4， and SYP mRNA levels （<italic>P</italic><0.05，<italic>P</italic><0.01）. In the low-dose Kaixinsan group， the stay time in the target quadrant was prolonged and the expression of hippocampal SYP mRNA was elevated significantly （<italic>P</italic><0.05）. There was no statistical difference in swimming speed between the groups. Conclusion:Kaixinsan can improve the learning and memory ability of APP/PS1 mice by increasing the expression of synaptic plasticity-related proteins， reducing the ultrastructural damage to hippocampal neurons， resisting oxidative stress， and regulating cholinergic neurotransmitters， thereby exerting neuroprotective effects.

Effect of electroacupuncture at governor vessel on learning-memory ability and serum level of APP, Aβ in patients with Alzheimer's disease / 中国针灸

OBJECTIVE@#To compare the therapeutic effect of electroacupuncture (EA) combined with donepezil hydrochloride and donepezil hydrochloride alone on improving learning-memory ability in patients with Alzheimer's disease (AD), and to explore its action mechanism.@*METHODS@#Sixty patients of AD were randomly divided into an observation group and a control group, 30 cases in each group. The patients in the observation group were treated with EA at governor vessel (GV) combined with donepezil hydrochloride. EA was applied at Baihui (GV 20) and Fengfu (GV 16) with dilatational wave (10 Hz/50 Hz of frequency, 0.5 to 5.0 mA of intensity), and the needles were kept for 40 min, EA was given once a day; the donepezil hydrochloride tablet was taken orally, 5 mg, once a day, and after 4 weeks the dosage might be increased to 10 mg per day according to the specific situation. All the treatment was given for 8 weeks. The patients in the control group were only treated with donepezil hydrochloride with the identical procedure as the observation group. The Montreal cognitive assessment (MoCA) and Alzheimer's disease assessment scale cognitive part (ADAS-Cog) were evaluated before and after treatment; P300 (latency and amplitude of N2 and P3) was detected by EEG/ERP system brain event related potential instrument, and amyloid precursor protein (APP) and β-amyloid protein 1-42 (Aβ) were detected by ELISA.@*RESULTS@#Compared before treatment, the MoCA scores were increased after treatment in the two groups (<0.05), and the MoCA score in the observation group was higher than that in the control group (<0.05). Compared before treatment, the ADAS-Cog scores were decreased after treatment in the two groups (<0.05), and the ADAS-Cog score in the observation group was lower than that in the control group (<0.05). Compared before treatment, the latency of N2 and P3 was shortened and the amplitude was increased after treatment in the two groups (<0.05); after treatment, the latency of N2 and P3 in the observation group was shorter than that in the control group and the amplitude was higher than that in the control group (<0.05). Compared before treatment, the serum levels of APP and Aβ were lower after treatment in the two groups (<0.05), and the serum levels of APP and Aβ in the observation group were lower than those in the control group (<0.05).@*CONCLUSION@#EA at Baihui (GV 20) and Fengfu (GV 6) combined with donepezil hydrochloride can effectively reduce the serum levels of APP and Aβ and improve the scores of MoCA and ADAS-Cog and the levels of N2 and P3 of P300 in AD patients, which has superior effect to donepezil hydrochloride alone in improving the learning-memory of AD patients.

Mechanism of Schisandrae Chinensis Fructus Lignans in Alleviating Learning and Memory Ability in D-galactose Aging Mice / 中国实验方剂学杂志

Objective:To study the effect of Schisandrae Chinensis Fructus lignans (SCL) on learning and memory ability of D-galactose（D-gal）-induced aging model mice. Method:ICR mice were randomly divided into 4 groups: normal group (distilled water, subcutaneous injection with normal saline), model group (distilled water, subcutaneous injection with 200 mg·kg-1D-gal), piracetam group (oral administration with 200 mg·kg-1 piracetam, subcutaneous injection with 200 mg·kg-1D-gal), low-dose SCL group (oral administration with 50 mg·kg-1·d-1 SCL, subcutaneous injection with 200 mg·kg-1·d-1 D-gal), medium-dose SCL group (oral administration with 100 mg·kg-1·d-1 SCL, subcutaneous injection with 200 mg·kg-1·d-1D-gal), high-dose SCL group (oral administration with 200 mg·kg-1·d-1 SCL, subcutaneous injection with 200 mg·kg-1·d-1 D-gal). The drugs were administered continuously for 10 weeks. Dark test and Morris water maze test were performed to observe the effect of SCL on the learning and memory ability of D-gal-induced aging mice. The activities of superoxide dismutase (SOD) and malondialdehyde (MDA) in mouse brain tissue were detected by chemical colorimetry. The expressions of peroxiredoxin-6（Prdx6） and glutathione peroxidase 1（GSH-Px1） mRNA in mouse brain tissue were detected by polymerase chain reaction (PCR). The expressions of Prdx6 and GSH-Px1 protein in mouse tissues were detected by Western blot. Result:In behavioral experiments, compared with normal group, the number of dark avoidance errors in model group significantly increased (P<0.05), the latency was significantly reduced (P<0.01), and the number of mouse passes and the target quadrant residence time were significantly reduced (P<0.01), which can be used as an indicator of successful modeling. Compared with the model group, the number of errors in the piracetam group, and medium and high-dose SCL groups was significantly reduced (P<0.05，P<0.01), and the latency was significantly prolonged (P<0.05，P<0.01). At the same time, the number of water maze passes and the target quadrant retention time in the high-dose SCL group increased significantly (P<0.01). The results of biochemical indicators showed that compared with normal group, the SOD activity in brain tissue of model group mice was significantly reduced (P<0.01), while the MDA content was increased (P<0.05). Compared with the model group, SOD activity in the brain tissues of piracetam group, and low, medium and high-dose piracetam groups was significantly increased (P<0.05), whereas the level of MDA was reduced (P<0.05). The expressions of Prdx6 and GSH-Px1 were significantly increased (P<0.05，P<0.01), indicating that the SCL administration group was dose-dependent. Conclusion:SCL can improve the learning and memory ability of D-gal-induced aging mice, which may be related to the anti-oxidation ability of SCL and the up-regulation of Prdx6 and GSH-Px1 expressions in mouse brain tissue.

Effects of PNU-282987 on neuronal apoptosis and learning and memory ability after cerebral ischemia-reperfusion in rats / 中国药科大学学报

@#To investigate the neuroprotective effect and possible molecular mechanism of PNU-282987 on rats subjected to ischemia and reperfusion. In this study, middle cerebral artery occlusion/reperfusion(MCAO/R)in rats was used as the animal model. The 44 Sprague-Dawley(SD)rats were divided into 4 groups, sham group, model group, low-dose of PNU-282987(1. 2 mg/kg)and high-dose of PNU-282987(2. 4 mg/kg)treatment group. Y-maze test was tested for the learning and memory abilities of rats, and we also examined the brain infarct size, brain edema and neurological dysfunction in rats. Furthermore, HE staining was used to evaluate the neuronal injury and TUNEL assay was used to evaluate the neuronal apoptosis in the rat brain. The results revealed that the learning and memory abilities of rats in treatment group improved significantly, and treatment with PNU-282987 reduced brain infarct size, lessoned brain edema, lessened neurological dysfunction, ameliorated pathological injury and prevented neuronal apoptosis. The above results suggest that the underlying mechanism of PNU-282987 on improving learning and memory abilities of rats after cerebral ischemia and reperfusion may include the inhibition of neuronal apoptosis.

Comparison of efficacy and mechanism of Compound Danshen Tablets and its decomposed prescriptions on learning and memory ability of rats with vascular dementia / 中草药

Objective: To compare the effect and mechanism of Compound Danshen Tablets and its disassembled prescription on learning and memory ability of rats with vascular dementia (VD). Methods: Rats with normal learning and memory ability were screened through the shuttle box, and then divided into seven groups: sham group, model group, contrast group (dihydroergotaminemesylate 0.65 g/kg), Danshen group (ethanol extract of Salvia miltiorrhiza 0.3 g/kg), Senqi group (Panax notoginseng powder 0.3 g/kg), Compound Danshen Tablets group (low dose 0.3 g/kg, high dose 0.6 g/kg), ig administration, once daily one time, after 7 d of continuous administration, the VD rat model was established by bilateral common carotid artery ligation and reperfusion. After 7 d of continuous administration, the shuttle box test and neurological deficit score were performed; TTC staining and Nissl staining were used to detect the area of cerebral ischemia and the pathological changes of rat in the cerebral cortex respectively. The changes of SOD, MDA, Ach, 5-HT in the brain and VEGF, ET, eNOS, IL-6 in the serum were detected by kit. Results: Compared with the model group, the Compound Danshen Tablets group increased the number of conditional stimulation avoidance in VD rats, reduced the neurological function score and cerebral ischemia area, and reduced the MDA in rat brain tissue and ET, eNOS, IL-6 in rat serum, and increased Ach, 5-HT, SOD in the brain and VEGF in the serum. S. miltiorrhiza extract had better performance in reducing MDA in rat brain tissue and ET, eNOS, IL-6 in rat serum, SOD in the brain than in P. notoginseng; P. notoginseng was more advantageous in improving the content of Ach and 5-HT in rat brain tissue. The high-dose group of Compound Danshen Tablets had significant differences in SOD, MDA, ACH, 5-HT, and VEGF compared with Danshen group or Senqi group (P < 0.05, P < 0.01). Conclusion: Compound Danshen Tablets can improve the cognitive learning and memory ability of VD rats. The mechanism maybe enhance the secretion of Ach by the central cholinergic nervous system, improve the content of the monoamine neurotransmitters 5-HT in the hippocampus and hypothalamus, reduce the lipid peroxidation damage of the brain tissue, inhibit the inflammatory injury reaction and promote angiogenesis. In the compound, S. miltiorrhiza extract as the role of “Jun medicine”, plays a major role, while P. notoginseng assists “Jun medicine” in treating VD.

Effects of Chinese herbal medicine of tonifying spleen and stomach on learning and memory ability and PKA/ERK/p-CREB pathway in hippocampus of SAMP8 mice / 中草药

Objective: To study the effects of prescriptions including Ginseng Decoction, Xixin Decoction, and Dabuyuan Decoction for tonifying spleen and stomach on learning and memory ability and PKA/ERK/p-CREB pathway in hippocampus of SAMP8 mice, and explore the mechanism in the prevention and treatment of Alzheimer's disease (AD). Methods: Three-month-old SAMP8 mice were randomly divided into model group, Donepezil Hydrochloride group, prescription group of Tonifying Spleen and Stomach Yuanqi Prescription (Ginseng, Xixin Decoction, and Dabuyuan Decoction). Moreover, three-month-old SAMR1 mice were recruited as a normal control group, six groups in total. Related indices were detected after 10 weeks continuous gastrogavage. The spatial learning-memory deficit of mice was detected by Morris water maze test. The expression levels of PKA protein in hippocampal region of mice were detected by immunohistochemistry, and the expression levels of ERK and p-CREB protein in hippocampal region of mice were detected by immunofluorescence. The protein expression levels of PKA, ERK, and p-CREB in hippocampus were detected by Western blotting. Results: Compared with the model group, the escape latency of the prescription group of tonifying spleen and stomach was decreased (P < 0.05, P < 0.01), while the swimming time and the times of crossing the platform in the target quadrant were increased (P < 0.01). Results of immunohistochemistry showed that the protein expression of PKA was significantly increased and the expression of ERK and p-CREB in hippocampal region was significantly increased (P < 0.05, P < 0.01). The results of Western blotting were consistent with those of immunohistochemistry and immunofluorescence (P < 0.05, P < 0.01). Conclusion: The Tonifying Spleen and Stomach Yuanqi Prescription showed obvious improvement on the spatial learning-memory deficit in SAMP8 mice, which might be associated with affecting the PKA/ERK/p-CREB pathway in hippocampal region.

Effects of Electroacupuncture on Learning and Memory Ability and Brain Inflammatory Factor in Rats with Vascular Cognitive Impairment / 中国中医药信息杂志

Objective To observe the effects of electroacupuncture on the learning and memory ability and cerebral cortex inflammatory factor of rats with vascular cognitive impairment (VCI); To discuss the mechanism of electroacupuncture for preventing and treating VCI. Methods VCI rat models were made in microemboli injection through internal carotid artery method. The successful modeled rats were randomly divided into model group, positive medicine group and electroacupuncture group, and normal rats were taken as control group. Three days after rat models were established, the positive medicine group was given donepezil hydrochlorideby gavage, and electroacupuncture group was given electroacupuncture at "Baihui" and "Zusanli" acupoints. After treatment, the learning and memory ability was detected by Morris water maze test. The contents of TNF-α, IL-6 and IL-1β in rat brain tissue were detected by ELISA. Results The water maze results showed that with the increase of the number of training, the average escape latency of rats to find platform in positive medicine group and electroacupuncture group all had different degrees of shortening in positioning cruise experiment; in space exploration experiment, positive medicine group and electroacupuncture group to cross the platform area for the first time were significantly reduced compared with the model group; compared with the control group, the contents of TNF-α, IL-6 and IL-1β in the model group were increased significantly; compared with the model group, the contents of TNF-α, IL-6 and IL-β in postive medicine group and electroacupuncture group were decreased. Conclusion Electroacupuncture at "Baihui"and "Zusanli" acupoints can decrease the contents of TNF-α, IL-1 and IL-6 in the cortex of VCI rats, and improve the learning and memory ability of rats.

Trillium Tschonoskii Maxim improves cognitive dysfunction in AD rats by inhibiting GSK-3βactivity, attenuating tau pathologies and promoting synaptic development / 中国药理学通报

Aim To assess the effects of Trillium Tschonoskii Maxim ( TTM ) decoction on Tau protein phosphorylation and synaptic development in AD model rats induced by high activity GSK-3β. Methods The SD rats were divided into five groups of ten animals, named sham-operated group ( blank group) , AD model group, TTM group (0. 5, 0. 25, 0. 125 g·kg-1 · d-1 ) . Treatment group received gavage once a day for seven days with TTM decoction, while other groups by gavage once a day for seven days with drinking water. On 2nd day by gavage, Morris water maze test was used to assess the spatial learning and memory ability of the rats. After five days' training, rats in the treat-ment groups and AD model group were injected wort-mannin ( WT, PI3K specific inhibitor ) and GF-109203X (GFX, PKC specific inhibitor) (100 μmol ·L-1 of each, total volume of 10 μL) into the right lateral ventricle. Western blot was used to detect the levels of phosphorylation Tau protein at multiple sites and the expression level of PI3K, Akt, PKC, GSK-3β(S9, T216) and synapse-associated proteins. Immu-nohistochemical method was used to detect the hyper-phosphorylation of Tau protein in hippocampus of rats. Golgi staining was applied to detect the number and morphological changes of synaptic development and dendritic spines. Nissl' s staining was employed to ob-serve the development of neonatal neurons in hippo-campus and cortex. Results Western blot showed that the phosphorylation level of Tau in hippocampus increased in model group, and the activity of GSK-3βwas up-regulated. Among them, however, in middle dose TTM group, the phosphorylation level of Tau in hippocampus decreased and the activity of GSK-3βde-creased. The expression levels of p-PKC and p-Akt in low and middle dose treatment group were higher than those in model group, thus increasing the activity of PKC and Akt to inhibit the activity of GSK-3β kinase. Immunohistochemistry also indicated that TTM could decrease the biological effects of Tau phosphorylation in hippocampus of AD rats. Western blot showed that TTM could increase the expression levels of synapsin-1 , syn-aptophysin and GluR-1 in hippocampus of AD rats. Nissl staining showed that the number of Nissl bodies in hippocampal neurons of AD model group were signif-icantly fewer than those of sham operation group, which could be increased by TTM middle and high dose group, and the complexity and dendritic spine density of hippocampal neurons in AD rats could be en-hanced as well. Conclusion TTM can effectively im-prove the cognitive function of AD rats induced by the increase of GSK-3β activity, and its possible mecha-nism may be via down-regulating the activity of GSK-3β and inhibiting the phosphorylation of tau protein and promoting the development of neurons.

Protective effect of curcumin on behavior and blood brain barrier in rat model of radiation injured brain / 实用医学杂志

Objective To observe the effect of curcumin on behavior,blood brain barrier(BBB)and ex-pression of glial fibrillary acidic protein(GFAP)and cyclic nucleotide 3′phosphohydrolase(CNPase)in hippocam-pus of radiation injured brain(RIB)rats. Methods SD rats were divided into radiation group,treatment group and negative control group. RIB rats model were established by X ray,and rats in treatment group were treated by curcumin. Morris water maze test were taken to study learning memory of rats in each group. The expression of Ev-ans blue(EB)in brain tissue and the expression of GFAP and CNPase in hippocampus were detected to observe the effect of curcumin on the BBB of RIB rats. Results In RIB rats,learning memory were decreased significant-ly,permeability of BBB were increased. GFAP expression in brain tissue was increased,and CNPase was de-creased(P < 0.05). After the treatment of curcumin,learning memory of rats were improved,the permeability of BBB was decreased,GFAP was decreased,and CNPase expression was increased(P < 0.05). Conclusion Cur-cumin can significantly reduce the damage of BBB in RIB rats,decrease the expression of GFAP and increase the expression of CNPase in hippocampal,which indicate that curcumin has curative effect on radiation injured brain.

Effects of Tiaoxin Formula on Spatial Learning and Memory Ability and LTP in Hippocampus of APP/PS1 Double Transgenic Mice with Alzheimer Disease / 中国中医药信息杂志

Objective To investigate the effects of Tiaoxin Formula on spatial learning and memory ability and long-term potentation (LTP) in the hippocampus of APP/PS1 transgenic mice with Alzheimer disease; To discuss its mechanism of action. Methods Totally 54 three-month-old APP/PS1 transgenic mice were randomly divided into model control group, Tiaoxin Formula group and positive control group, with 18 mice in each group. Another 18 three-month-old C57BL/6J wild mice were chosen as normal control group. All administration groups receive relevant medicine. 12 weeks later, Morris water maze test was used to test behavior and in vitro electrophysiology record. Results The Morris water maze test showed that in place navigation test, compared with the model control group, escape latency time in Tiaoxin Formula group was significantly reduced (P0.05). Conclusion Tiaoxin Formula can improve the spatial learning and memory ability and LTP of APP/PS1 transgenic mice with Alzheimer disease, thus can realize cognitive protection effects.

Banqiao Codonopisis Pilosula improves cognitivedysfunction induced by high GSK-3β activity and its possible mechanism / 中国药理学通报

Aim To assess the effects of Banqiao Codonopisis Pilosula(BCP)decoction on learning and memory dysfunction in AD model rats induced by high activity GSK-3β and its possible mechanism.Methods The SD rats(4 months old,♂)were divided into five groups,namely,sham-operated group(blank group),AD model group,BCP high-dose(2.16 g·kg-1·d-1)group,BCP medium-dose(1.08 g·kg-1·d-1)group,and BCP lower-dose(0.54 g·kg-1·d-1)group.Treatment group received BCP decoction by gavage once a day for 14 days,while other groups were offered drinking water by gavage once a day for 14 days.The autonomous behavior activities of all rats were observed and recorded after gavage.In the last seven days by gavage,Morris water maze test was used to test the spatial learning and memory ability of the five groups.After five days training,treatment groups and AD model group were injected wortmannin(WT,PI3K specific inhibitor)and GF-109203X(GFX,PKC specific inhibitor)(100 μmol·L-1 of each,total volume of 10 μL)into the right lateral ventricle of the rats.The blank group was only injected 2％DMSO.The spatial memory retention was detected by water maze 24 hours after lateral ventricle injection.Then,changes in the spatial learning memory of rats were observed.The level of Tau phosphorylation in SD rat hippocampus and the expression and activity changes of related protein kinase GSK-3β were detected by Western blot and immunohistochemistry.The changes of Nissl bodies in SD rat hippocampus were observed by Nissl′s staining.Results After intragastric administration of BCP,the rat autonomous behavior activities in each group all showed a declining trend,and the differences in low-dose and middle-dose groups had statistical significance compared with blank group.The Morris water maze tests showed that the latency navigation of model group was significantly longer than that of blank group(P<0.01),while that of the BCP three doses groups was shorter than that of model group(P<0.05).Compared with the same group,the latency navigation of the three groups after gavage BCP low,middle and high dose was significant shorter than that without gavage(P<0.05).Western blot results showed that the activity of GSK-3β in AD model group was up-regulated compared with the blank group.However,BCP inhibited activity of GSK-3β.Western blot and immunohistochemistry results showed the level of Tau phosphorylation in AD model group was increased compared with the blank group in the area of CA3(P<0.05).Compared with AD model group,the level of Tau phosphorylation was decreased in treatment group.Nissl′s staining results showed that dendritic spines in AD model group was significantly attenuated compared with the blank group(P<0.05).Far more dendritic spines were observed in treatment group than in AD model group.The number of Nissl′s bodies in neuron cells of hippocampus in hippocampal CA3 was obviously larger in treatment groups than in AD model group.These effect of BCP was dose-dependent.Conclusions BCP can prevent the learning and memory dysfunction in AD model rats induced by high activity of GSK-3β.The mechanism may be related to inhibiting GSK-3β activity and then reducing the level of phosphorylation of Tau and improving neural development.

Aβ25-35 protein in different concentrations to create a rat model resembling Alzheimer's disease and the differences in their learning and memory ability / 中国比较医学杂志

Objective To observe the learning and memory ability of rats after injection of Aβ25-35 protein in different concentrations into the lateral ventricle assessed by Morris water maze test, and to explore the optimal concentration of Aβ25-35 in the preparation of AD model rats.Methods Male SD rats were randomly divided into sham operated group and model group.The rats of model group received Aβ25-35 injection in concentrations of 2 μg/μL, 4 μg/μL and 8 μg/μL, respectively.According to the Rat Brain Stereotaxic Atlas, 5 μL of aggregation of Aβ25-35 was injected into the right lateral ventricle to establish the AD rat model.7 days after successful modeling, Morris water maze was used to test thechanges of learning and memory ability of the rats.Results There was no significant difference in the average swimming speed between the two groups (P > 0.05).The escape latency time of rats in the model group was significantly increasedcompared with the sham group (P 0.05).The activity time and distance of target quadrant of the rats injected with different concentration of Aβ25-35in the model group were significantly reduced compared with the sham group (P 0.05).Compared with the sham-operated group, the number of platform-crossing of rats injected with different doses of Aβ25-35in the model group were significantly reduced (P 0.05).Conclusions The recommended dose and concentration of Aβ25-35 to be injected into the unilateral ventricle to establisha rat model of Alzheimer's disease is 4 μg/μL in a volume of 5 μL.

Effects and mechanisms of different frequencies of electroacupuncture for learning and memory ability of Alzheimer's rats / 中国针灸

<p><b>OBJECTIVE</b>To observe the effects of different frequencies of electroacupuncture (EA) at "Baihui (GV 20)" and "Shenshu(BL 23)" for the learning and memory ability as well as glycogen synthase kinase-3β (GSK-3β) and growth associated protein-43 (GAP-43) in hippocampal tissue of rats with Alzheimer's disease(AD), so as to explore the mechanism of different frequencies of EA for the prevention and treatment of AD.</p><p><b>METHODS</b>One hundred and twelve healthy Wistar male rats were divided into seven groups by random number table, namely a normal group, a sham operation group, a model group, an acupuncture group, a 2 Hz EA group, a 30 Hz EA group, and a 50 Hz EA group, 16 rats in each one. The rats in the normal group were conventionally raised in the laboratory without any treatment. 0.9% NaCl solution was injected into bilateral dentate convolution of hippocampus in rats of the sham operation group. AD model was established by β-amyloid protein1-42 (Aβ1-42) injected into bilateral dentate convolution of hippocampus in the other groups. 15 days after establishment, no treatment was applied in the model and sham operation groups, and EA with corresponding frequencies at "Baihui (GV 20)" and "Shenshu (BL 23)" was used in the three EA groups for 2 sessions, once a day and 7 times as one session. There was 1 day between the two sessions. The same acupoints were adopted in the acupuncture group, without electrical connection. The escape latency, the first spanning platform time, and the number of crossing platform were tested in the Morris water maze immediately after treatment. The expressions of GSK-3β and GAP-43 were examined by immunohistochemistry and Western blot.</p><p><b>RESULTS</b>①Morris water maze tests showed that the escape latency and the first spanning platform time significantly increased in the model group compared with those in the normal group (both<0.01), and the number of crossing platform decreased (<0.01). Compared with the model group, the escape latency and the first spanning platform times decreased in the acupuncture and three EA groups (all<0.01), and the numbers of crossing platform increased (<0.01). Compared with the acupuncture and 2 Hz, 30 Hz EA groups, the escape latency decreased in the 50 Hz EA group (<0.01,<0.05); the first spanning platform time reduced (all<0.01); the number of crossing platform increased (<0.01,<0.05). ②The expressions of GSK-3β and GAP-43 of the model group increased compared with those of the normal group(both<0.01). The expressions of GSK-3β in the acupuncture and three EA groups decreased compared with that in the model group (all<0.01), and the expressions of GAP-43 increased (all<0.01). The expressions of GSK-3β decreased and GAP-43 increases in the 50 Hz EA group compared with those in the acupuncture group and 2 Hz, 30 Hz groups (all<0.01).</p><p><b>CONCLUSIONS</b>EA may promote synaptic damage rehabilitation by down regulating GSK-3β and up regulating GAP-43 to improve learning and memory ability of AD rats. The effect of 50 Hz EA is better than those of 30 Hz and 2 Hz EA and acupuncture.</p>

Research of Ginsensode Rg1 on the Expression of Neurogranin and Behavioral Alteration in Chronic Unpredictable Stress Model Rats / 昆明医科大学学报

Objective To investigate the effect of Ginsensode Rgl on the expression of Neurogranin (Ng) and behavioral alteration in cortex and hippocampus of rats with chronic stress model.Methods A total of 36 adult male SD rats were randomly divided into control group (CON),model group (CUS) and treatment group (CUS-G).The chronic stress model was established by chronic unpredictable stress.The Morris water maze was used to study the learning and memory ability.The content of Ng in cortex,hippocampus was detected by RT-PCR and Western blot.Results The water maze test showed that after chronic stress,animal learning and memory ability decreased significantly,while the treatment group rats escape latency was significantly reduced (P＜0.05);after 6 weeks of stress,the cortex and hippocampus Ng mRNA levelschronic stress rats were markedly lower than that of model rats respectively (P＜0.05,P＜0.01,P＜0.05).The cerebral cortex and hippocampus Ng mRNA levels in treatment group were significantly increased compared with that of model group respectively (P＜0.01,P＜ 0.05,P＜0.05);The cerebral cortex and hippocampus Ng levels of chronic stress rat were significantly decreased when compared with that of the model rats respectively (P＜0.05,P＜0.01,P＜0.05),The cerebral cortex and hippocampus Ng content were significantly increased in treatment group compared with the model group respectively (P＜0.01,P＜0.05).Conclusions Chronic stress can change the behaviors of nice in recognization and memory The contents of Ng and the supplement of Ginsensode Rg1 have positive adjustment.

Effects of Exercise Training on Learning and Memory Ability and Diffusion Tensor Imaging in Rats after Focal Cerebral Ischemia / 中国康复理论与实践

Objective To explore the effect of exercise training on learning and memory ability in rats with focal cerebral ischemia, and to analyze the changes of brain tissue structure of rats after exercise training through diffusion tensor imaging (DTI). Methods Twenty-four SPF male Sprague-Dawley rats were randomly divided into sham operation group (n=8), natural recovery group (n=8) and exercise training group (n=8). The left middle cerebral artery occlusion (MCAO) model was established. The exercise training group received running wheel training 24 hours after modeling, for 14 days. All groups were tested by the Morris water maze 15 days after modeling. The latency in the navigation experiment, as well as the first latency, boundary swimming time ratio, the boundary swimming distance ratio, the average speed and the swimming path in the space exploration experiment were recorded. Four rats with similar Longa scores in each group received rou-tine magnetic resonance imaging and DTI scanning, the fractional anisotropy (FA), axial diffusivity (λ‖), and radial diffusivity (λ⊥) of isch-emic cortex and hippocampal lesion and contralateral side were measured. Results In the navigation experiment, the latency of three groups showed a downward trend along with training days (P0.05), while it was shorter in the exercise train-ing group than in the natural recovery group in the same time (P2.627, P2.521, P0.05). The swimming paths in the exercise training group and the sham operation group were better than that of the natural recovery group. The FA and rFA in the left cortical area were higher in the sham operation group than in the exercise training group and the natural recovery group (P0.05). There was no significant difference in the FA in the right cortical area among three groups (F=0.532, P=0.607). Theλ⊥,λ‖, rλ‖and rλ⊥in the left cortical area were lower in the sham opera-tion group than in the natural recovery group (P0.05). There was no significant difference in theλ⊥andλ‖in the right cortical area among three groups (F0.05). There was no significant difference in the FA,λ⊥,λ‖and rFA, rλ⊥and rλ‖in the bilateral hippo-campal interest area among three groups (F0.05). The rFA, rλ‖, rλ⊥and leftλ⊥ were correlated with the latency in the space ex-ploration experiment in the Morris water maze test (P<0.05), in which the correlation coefficient of rλ⊥was the highest (r=0.761, P<0.01). Conclusion Proper exercise training can improve the learning and memory ability of rats with focal cerebral ischemia, and can promote the repair of nerve fiber damage and reduce the vascular edema. In addition, the rFA, rλ‖, rλ⊥andλ⊥of ischemic cortex may be predictors of cognitive function recovery in rats after focal cerebral ischemia, especially rλ⊥.

Effects of Suanzaoren Decoction on Learning and Memory Ability and Brain Neurotransmitters Content of Senile Insomnia Model Rats / 中国药房

OBJECTIVE:To study the effects of Suanzaoren decoction on learning and memory ability and brain neurotransmit-ters content of senile insomnia model rats. METHODS:Rats were randomly divided into normal group,model group,positive group [Estazolam tablet,2 × 10-3 g/(kg·d)] and Suanzaoren decoction low-dose,middle-dose and high-dose groups [5,10,15 g/(kg·d)],with 10 rats in each group. Except for normal group,those groups were given D-galactose ih on the back+sleep depriva-tion to induce senile insomnia model. 6 weeks after modeling,treatment groups were given relevant medicine intragastrically for one week,and normal group and model group were given normal saline intragastrically. The escape latency,the percentage of swimming time and the time of original platform crossing were observed,and the contents of Glu and GABA in cerebral tissue were determined as well as the contents of IL-1β and 5-HT in hypothalamus. RESULTS:Compared with normal group,escape la-tency of rats prolonged and the contents of IL-1β and 5-HT in hypothalamus decreased,while the percentage of swimming time of original platform quadirant,the time of original platform crossing and the contents of Glu and GABA in cerebral tissue increased (P<0.05). Compared with model group,above index of treatment groups improved significantly,with statistical significance(P<0.05). Compared with positive group,the changes of above index were more significant in Suanzaoren decoction middle-dose and high-dose groups,with statistical significance (P<0.05). CONCLUSIONS:Suanzaoren decoction could markedly enhance the learning and memory ability of senile insomnia model rats,and reduce neurotransmitters content and relieve the delayed neuronal damage which led by Glu and GABA.

Effects of neonatal repeated inha lation of sevoflurane on ability of learning and memory and hippocampal volume in infantile rats / 医学研究生学报

Obj cetive A large number of recent studies show that sevoflurane anesthesia may cause learning and memory dysfunction.The aim of this study was to explore changes of learning and memory ability and hippocampal volume in infantile rats after neonatal interrupted and repeated inhalation of 2.6% sevoflurane through detecting the learning and memory ability by Morris water maze and the hippocampus volume by MRI.Method s Thirty two neonatal SD rats were randomly devided into two groups (n=16):experimental group and control group.Rats inhalated 2.6%sevoflurane in the experimental group and 1 L/min O2 +1 L/min Air in the control group at the postnatal days of 7, 14 and 21 (P7, P14, P21). The learning and memory ability was determined by the Morris water maze test from P31 to P37;The brains of rats were scanned by mag-netic resonance imaging ( MRI) machine under anesthesia with 1%sodium pentobarbital at P37, and the brain and bilateral hippocampal volumes were measured. Results ①In the place navigation test, the escape latency had no significant difference between the two groups (P>0.05).In the spatial probe test, the dwelling time, movement distance and number of entering times in platform quadrant decreased slightly in experimental group compared with those in the control group, while there was no significant difference (P>0.05).②The brain volume [(1.53 ±0.18) cm3 vs (1.60 ±0.13) cm3] and right hippocampal volume [(16.15 ±1.76)mm3 vs(16.46 ±1.71)mm3] had no significant difference between the two groups (P>0.05).The left hippocampal volume [(16.46 ±1.71)mm3] was decreased in the experimental group compared with the control group [(18.10 ±2.53)mm3](P<0.05). Conclusion The learning and memory ability has no significant changes in in-fantile rats after neonatal interrupted and repeated sevoflurane inhalation and MRI examination of hippocampal volume is not sufficient for the diagnosis of cognitive dysfunction.